Shiga University of Medical Science Repository BI WAKO / 滋賀医科大学機関リポジトリ
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Pro- and anti-inflammatory roles of interleukin (IL)-33, IL-36, and IL-38 in inflammatory bowel disease
No full textInterleukin-33 (IL-33), IL-36, and IL-38 are members of the IL-1 cytokine family. The expression of each cytokine has been reported to be increased in the inflamed mucosa of patients with inflammatory bowel disease (IBD). IL-33 and IL-36 have been studied for pro- and anti-inflammatory functions, and IL-38 has been characterized as an anti-inflammatory cytokine by antagonizing the IL-36 receptor (IL-36R). IL-33 is a nuclear cytokine constitutively expressed by certain cell types such as epithelial, endothelial, and fibroblast-like cells and released on necrotic cell death. IL-33 mainly induces type 2 immune response through its receptor suppression tumorigenicity 2 (ST2) from Th2 cells and type 2 innate lymphoid cells (ILC2s), but also by stimulating Th1 cells, regulatory T cells, and CD8+ T cells. IL-36 cytokines consist of three agonists: IL-36α, IL-36β, and IL-36γ, and two receptor antagonists: IL-36R antagonist (IL-36Ra) and IL-38. All IL-36 cytokines bind to the IL-36R complex and exert various functions through NF-κB and mitogen-activated protein kinase (MAPK) pathways in inflammatory settings. IL-33 and IL-36 also play a crucial role in intestinal fibrosis characteristic manifestation of CD. In this review, we focused on the current understanding of the pro- and anti-inflammatory roles of IL-33, IL-36, and IL38 in experimental colitis and IBD patients.Journal Articlejournal articl
Isolation of TCR genes with tumor-killing activity from tumor-infiltrating and circulating lymphocytes in a tumor rejection cynomolgus macaque model
Get PDFpdfTo develop effective adoptive cell transfer therapy using T cell receptor (TCR)-engineered T cells, it is critical to isolate tumor-reactive TCRs that have potent anti-tumor activity. In humans, tumor-infiltrating lymphocytes (TILs) have been reported to contain CD8+PD-1+ T cells that express tumor-reactive TCRs. Characterization of tumor reactivity of TILs from non-human primate tumors could improve anti-tumor activity of TCR-engineered T cells in preclinical research. In this study, we sought to isolate TCR genes from CD8+PD-1+ T cells among TILs in a cynomolgus macaque model of tumor transplantation in which the tumors were infiltrated with CD8+ T cells and were eventually rejected. We analyzed the repertoire of TCRα and β pairs obtained from single CD8+PD-1+ T cells in TILs and circulating lymphocytes and identified multiple TCR pairs with high frequency, suggesting that T cells expressing these recurrent TCRs were clonally expanded in response to tumor cells. We further showed that the recurrent TCRs exhibited cytotoxic activity to tumor cells in vitro and potent anti-tumor activity in mice transplanted with tumor cells. These results imply that this tumor transplantation macaque model recapitulates key features of human TILs and can serve as a platform toward preclinical studies of non-human primate tumor models.Journal Articlejournal articl
Gastric emptying capacity test by 13C breath test using semi-solid test meal : Report of preliminary data by healthy volunteers
Get PDFpdf背景：
胃癌の治療においては根治切除手術が必要不可欠であるが、近年は早期胃癌、高齢者の増加に加え、腹腔鏡手術やロボット支援下手術による低侵襲化が進んでいる。一方で胃切除術後の体重減少やダンピング症候群などの生活の質を低下させる「胃切除後障害」が問題となっている。
目的：
本試験は流動食のみでなく実際に患者が食すであろう食事にできるだけ近づけた形態の半固形食を作成し、健常volunteerに服用してもらい13C-acetate呼気試験を行うことで胃排出能の評価を行うことである。方法：試験は過去に行われた同様の13C-acetate呼気試験と同様に行い、食事は半固形食を使用することで過去の報告の液状食、固形食との胃排出速度との違いを比較した。
結果：
健常volunteerは年齢45(40–58)歳、男性:女性=5:15、BMI 23.1(20.2-30.5) kg/m2。Cmaxの中央値は32.4 (16.2 – 44.1) (‰), T1/2の中央値は36.8 (13.0 – 75.4)分であった。試験食摂取前から摂取240分までの呼気中の13CO2排出変化量を測定したところ、ピークは摂取後60分であった。過去の同様の研究報告と比較すると、液状食でピークは摂取後30分、固形食では80分といずれとも異なる結果であった。
結語：
健常volunteerにおいて半固形食を摂取した後の胃排出能は固形食、液状食いずれの結果とも異なるものであった。Background:
Radical resection surgery is essential in the treatment of gastric cancer. However, in recent years, in addition to an increase in the number of early-stage gastric cancers and elderly patients, minimally invasive surgery using laparoscopic or robotic gastrectomy has become popular. With this, post-gastrectomy syndromes that reduce patients’ quality of life, such as weight loss and dumping syndrome, have become a problem. However, the mechanism responsible for these disorders remains unclear.
Purpose:
In this study, we prepared not only a liquid diet but also a semi-solid diet that was as close as possible to the actual diet that patients would eat. Materials and Methods: The 13C-acetate breath test was performed as described in other studies with a semi-solid diet, and the difference in gastric evacuation rate between the liquid and solid diets reported in previous studies was compared.
Results:
Forty-five healthy volunteers were included (age range: 40–58 years, male: female = 5:15, Body Mass Index [BMI] 23.1 [range: 20.2–30.5] kg/m2). The median Cmax and median T1/2 was 32.4 (range: 16.2–44.1) ‰ and 36.8 (range: 13.0–75.4) minutes, respectively. The change in 13CO2 emission in exhaled air from before to 240 minutes after ingestion of the test meal was measured, with the peak being 60 minutes after ingestion. A similar study reported the peaks occurred 30 and 80 minutes after ingestion for the liquid and solid diets, respectively.
Conclusion:
Gastric emptying in healthy volunteers after ingestion of a semi-solid diet differed from that after ingestion of solid or liquid diets—the original diets. In the future, more gastric cancer patients must be evaluated in comparative studies.Departmental Bulletin Paperdepartmental bulletin pape
Predictors and clinical impact of postoperative diarrhea after colorectal cancer surgery: a prospective, multicenter, observational study (SHISA-1602)
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Postoperative diarrhea, including high-output stoma (HOS), frequently occurs after colorectal surgery; its risk factors and clinical implications on subsequent complications remain unknown. This study aimed to evaluate the risk factors and clinical implications of postoperative diarrhea after primary colorectal cancer (CRC) surgery.
Methods:
This prospective observational study included patients with CRC who underwent radical surgery at six hospitals between June 2016 and December 2017. The patients were categorized into three groups (non-stoma, colostoma, and ileostoma groups).
Results:
A total of 178 patients participated in the study. In the non-stoma group, the incidence of postoperative diarrhea was 18.4% (27/147). The incidence of HOS was 28.6% (4/14) in the ileostoma group, and 0% in the colostoma group. Multivariable analyses of the incidence of diarrhea in the non-stoma group indicated that habitual smoking and hypertension were significantly associated with postoperative diarrhea (P = 0.012 and P = 0.0274, respectively). Postoperative diarrhea was more likely to occur in patients with rectal cancer than in those with colon cancer (P = 0.0501). In the non-stoma and ileostoma groups, the probability of the occurrence of other complications with Clavien-Dindo (C-D) grades II or higher was significantly higher in patients with C-D grade I diarrhea, including HOS, than in patients without diarrhea (39.3% vs. 14.6%, P = 0.0061).
Conclusions:
Smoking and hypertension are the independent predictors of postoperative diarrhea after an elective CRC surgery. Rectal cancer surgery seems to be associated with postoperative diarrhea more than colon cancer surgery does. Mild postoperative diarrhea may lead to more severe complications.journal articl
Efficacy, safety, and optimal timing of single-trocar video-assisted flexible thoracoscopic debridement under local anesthesia for complicated parapneumonic empyema.
No full textObjective:
Thoracoscopic debridement under local anesthesia is a useful approach for complicated parapneumonic effusion or empyema (CPE) and is a less invasive procedure than video-assisted thoracoscopic surgery under general anesthesia. There are various methods of thoracoscopic debridement under local anesthesia, although the optimal timing of treatment is unknown. The objective of this study was to verify the efficacy and safety of our video-assisted flexible thoracoscopic debridement (VAFTS-D) procedure under local anesthesia, and to investigate the clinical features associated with the success of VAFTS-D.Methods:
The study included 71 consecutive patients with CPE who underwent VAFTS-D. The primary outcome was success of VAFTS-D. We retrospectively analyzed the efficacy and safety of VAFTS-D from the clinical data obtained from hospital medical records, and used univariate logistic analyses to identify potential predictors of the outcome.Results:
VAFTS-D was considered successful in 62 of 71 patients (87.3%). Two of the remaining nine patients died and the other seven patients required subsequent operation under general anesthesia. Complications due to VAFTS-D occurred in six patients (8.5%). Duration of empyema < 10 days (P = 0.024) and negative bacterial culture in pleural effusion (P = 0.029) were independently associated with the success of VAFTS-D by univariate logistic regression analysis.Conclusion:
VAFTS-D might be an acceptable first-line procedure in patients with suspected CPE. VAFTS-D should be performed as early as possible for a successful outcome, and to obtain useful information on the pleural cavity.Journal Articlejournal articl
Changes in fetal growth restriction and retinopathy of prematurity during the coronavirus disease 2019 pandemic: A cross-sectional study
Get PDFpdfPurpose:
To investigate changes in the number of preterm infants, low birth weight infants, and infants with fetal growth restriction (FGR) or retinopathy of prematurity (ROP) during the coronavirus disease 2019 (COVID-19) pandemic.Methods:
In this retrospective cross-sectional study, we reviewed the medical records of infants born and admitted to the neonatal intensive care unit and growth care unit of Shiga University of Medical Science Hospital before the COVID-19 pandemic (April 1, 2019 to September 30, 2019) and during the pandemic (April 1, 2020 to September 30, 2020). Medical records of infants’ mothers were also collected. Preterm infants, low birth weight infants, infants with FGR, infant and maternal factors associated with FGR, and infants requiring treatment for ROP were compared between the two periods.Results:
There were fewer infants born at < 28 weeks of gestation, infants with birth weight < 1,500 g, and infants with FGR during the pandemic period than the pre-pandemic period (pre-pandemic: n = 4 vs. during pandemic: n = 0, P = 0.048; pre-pandemic: n = 15 vs. during pandemic: n = 6, P = 0.02; and pre-pandemic: n = 31 vs. during pandemic: n = 12, P = 0.0002, respectively). There were no significant differences in any infant or maternal factors associated with FGR. The number of infants requiring treatment for ROP decreased during the pandemic, although this difference was not statistically significant (pre-pandemic: n = 3 vs. during pandemic: n = 0, P = 0.08).Conclusions:
Our findings showed a reduction in the number of infants with FGR during the COVID-19 pandemic. The number of infants born at < 28 weeks of gestation and infants with birth weight < 1,500 g also decreased during the pandemic period. There was a trend toward fewer infants requiring treatment for ROP during the COVID-19 pandemic.Journal Articlejournal articl
Case report : Vascular graft infection due to Aspergillus species presenting with recurrent vascular occlusion
Get PDFpdfBackground:
An aortic graft implantation is an effective therapeutic method for various aortic diseases. However, it is known that sometimes these implanted grafts can be the foci of infections. Here we report a rare case of graft infection that presented multiple embolisms of aortic branches and peripheral organs.Case presentation:
A 63-year-old Japanese woman with a history of aortic graft implantation presented with occlusions of large arteries in different loci and time points, with elevation of non-specific inflammatory markers. Thoracic contrast-computed tomography (CT) captured vegetation in the descending aortic graft and the [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) showed accumulation of FDG in the same site, suggesting a graft infection. Despite all these suspicious findings, repeated blood culture examinations never detected any microorganisms. A diagnosis of Aspergillus graft infection was made based on an elevated serum β-D glucan (βDG) and a positive Aspergillus galactomannan (GM) antigen test. The patient subsequently had surgery with replacement of the descending aortic graft and anti-fungal drugs were instituted with significant improvement noted.Conclusion:
In the present case, the patient's specific feature in the anatomical vascular construction, past operation, and basal fundamental diseases collaboratively contributed to the pathogenesis of the present infection. It is important to recognize the risk of graft infection and conduct imaging studies when indicative symptoms emerge. The negativity in blood culture studies often makes detection of pathogenic microbes extremely difficult. This case suggests that non-cultural tests such as bDG and GM can be useful for diagnosis and starting appropriate anti-fungal drugs in the early stages.Journal Articlejournal articl
Failure of DNA double-strand break repair by tau mediates Alzheimer's disease pathology in vitro
Get PDFpdfDNA double-strand break (DSB) is the most severe form of DNA damage and accumulates with age, in which cytoskeletal proteins are polymerized to repair DSB in dividing cells. Since tau is a microtubule-associated protein, we investigate whether DSB is involved in tau pathologies in Alzheimer's disease (AD). First, immunohistochemistry reveals the frequent coexistence of DSB and phosphorylated tau in the cortex of AD patients. In vitro studies using primary mouse cortical neurons show that non-p-tau accumulates perinuclearly together with the tubulin after DSB induction with etoposide, followed by the accumulation of phosphorylated tau. Moreover, the knockdown of endogenous tau exacerbates DSB in neurons, suggesting the protective role of tau on DNA repair. Interestingly, synergistic exposure of neurons to microtubule disassembly and the DSB strikingly augments aberrant p-tau aggregation and apoptosis. These data suggest that DSB plays a pivotal role in AD-tau pathology and that the failure of DSB repair leads to tauopathy.Journal Articlejournal articl
Characterization of a Conformation-Restricted Amyloid β Peptide and Immunoreactivity of Its Antibody in Human AD brain
Get PDF滋賀医科大学博士（医学）pdfThesis or DissertationACS chemical neuroscience. 2021 Sep 15;12(18):3418-3432.令和3年度thesi
Factors Influencing Pregnant Women's Injuries and Fetal Loss Due to Motor Vehicle Collisions: A National Crash Data-Based Study
Get PDF滋賀医科大学博士（医学）pdfThesis or DissertationHealthcare (Basel). 2021 Mar 3;9(3):273.令和3年度thesi